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Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways
- Source :
- Pharmacological Research. 53:113-122
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- Piceatannol is an anti-inflammatory and anti-proliferative plant-derived stilbene. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme to activate by various phytochemicals. In this study, we examined the ability of piceatannol to upregulate HO-1 expression in endothelial cells. We found piceatannol at micromolar (10-50 microM) concentrations dramatically increased HO-1 protein levels in a time-dependent manner. Piceatannol was similarly potent in the induction of HO-1 as hemin, arsenate, and 15d-PGJ2, and was more potent than some other phytochemicals including curcumin, EGCG, baicalein, and quercetin. In contrast, the similar chemical structure compounds, trans-stilbene, stilbene oxide, and resveratrol had no HO-1-inducing effects, suggesting a critical role for the hydroxyl groups in HO-1 induction. No cytotoxicity and superoxide production was observed after 10-50 microM piceatannol treatments. Piceatannol-mediated HO-1 induction was abrogated in the presence of N-acetylcysteine and glutathione, but not by other antioxidants. Induction of HO-1 by piceatannol was further enhanced by using buthionine sulfoximine. In addition, we determined that tyrosine kinase was involved in the induction of HO-1 by using tyrosine kinase inhibitors, herbimycin A, erbstatin, and genistein; in contrast, no significant changes in the pretreatment of PI3 kinase or MAP kinase inhibitors was determined. HO-1 induction was blocked by the protein kinase C inhibitors calphostin C, rottlerin, and long PMA pretreatment, whereas conventional PKC inhibitors, Go6976, and Ca2+ chelator BAPTA/AM, had no effect. Elevated HO-1 protein levels were associated with the inhibition of tumor necrosis factor-alpha (TNFalpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression. Treating ECs with zinc protoporphyrin, an HO-1 inhibito blocked the anti-inflammatory effect of piceatannol. In summary, this study identified piceatannol as a novel phytochemical inducer of HO-1 expression and identified the mechanisms involved in this process.
- Subjects :
- Cell Survival
Blotting, Western
Gene Expression Regulation, Enzymologic
chemistry.chemical_compound
Superoxides
Stilbenes
Animals
Buthionine sulfoximine
RNA, Messenger
Cells, Cultured
Protein Kinase C
Protein kinase C
Pharmacology
Piceatannol
biology
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Kinase
Protein-Tyrosine Kinases
Intercellular Adhesion Molecule-1
Molecular biology
Up-Regulation
Heme oxygenase
Calphostin C
chemistry
Enzyme Induction
Mitogen-activated protein kinase
Luminescent Measurements
biology.protein
Cattle
Endothelium, Vascular
Tyrosine kinase
Heme Oxygenase-1
Subjects
Details
- ISSN :
- 10436618
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Pharmacological Research
- Accession number :
- edsair.doi.dedup.....9c33c67fa1dda224cf4f1ade968a187e